Multilineage differentiation of human mesnchymal stem cells in a three-dimensional nanofibrous scaffold

Thomas Jefferson University, Filadelfia, Pennsylvania, United States
Biomaterials (Impact Factor: 8.56). 10/2005; 26(25):5158-66. DOI: 10.1016/j.biomaterials.2005.01.002
Source: PubMed


Functional engineering of musculoskeletal tissues generally involves the use of differentiated or progenitor cells seeded with specific growth factors in biomaterial scaffolds. Ideally, the scaffold should be a functional and structural biomimetic of the native extracellular matrix and support multiple tissue morphogenesis. We have previously shown that electrospun, three-dimensional nanofibrous scaffolds that morphologically resemble collagen fibrils are capable of promoting favorable biological responses from seeded cells, indicative of their potential application for tissue engineering. In this study, we tested a three-dimensional nanofibrous scaffold fabricated from poly(epsilon-caprolactone) (PCL) for its ability to support and maintain multilineage differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in vitro. hMSCs were seeded onto pre-fabricated nanofibrous scaffolds, and were induced to differentiate along adipogenic, chondrogenic, or osteogenic lineages by culturing in specific differentiation media. Histological and scanning electron microscopy observations, gene expression analysis, and immunohistochemical detection of lineage-specific marker molecules confirmed the formation of three-dimensional constructs containing cells differentiated into the specified cell types. These results suggest that the PCL-based nanofibrous scaffold is a promising candidate scaffold for cell-based, multiphasic tissue engineering.

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    • "In the current paradigm, the cellularcomponent is derived from stem cells that are induced to continually renew and that when directed have the potential to differentiate into chondrocytes and make cartilage. Several groups have used bone marrow-derived stem cells89909192, adipose-derived stem cells939495and blood-acquired mesenchymal progenitors[96]to various degrees of efficacy. Observations in developmental biology indicate that, for true 'like for like' replacement , tissue-specific stem cell sources are needed. "
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    ABSTRACT: Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.
    Full-text · Article · Dec 2016 · Stem Cell Research & Therapy
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    • "During the cell fate determination process, stem cells sense and react to physical properties of their microenvironment. Accordingly , some cell fates are reached only in three-dimensional (3-D) cell cultures [11] [12]. To date, in spite of extensive research efforts to control stem cell differentiation, the efficiency achieved in lineagerestricted differentiation is often poor. "
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    ABSTRACT: A large number of lineage-committed progenitor cells are required for advanced regenerative medicine based on cell engineering. Due to their ability to differentiate into multiple cells lines, multipotent stem cells have emerged as a vital source for generating transplantable cells for use in regenerative medicine. Increment in differentiation efficiency of the mesenchymal stem cell was obtained by using hydrogel to adjust the proliferation cycle of encapsulated cells to signal sensitive phase. Three dimensional (3-D) polymer networks composed of poly(2-methacyloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-p-vinylphenylboronic acid (VPBA)) (PMBV) and poly(vinyl alcohol) (PVA) were prepared as a hydrogel. The proliferation of cells encapsulated in the PMBV/PVA hydrogel was highly sensitive to the storage modulus (G') of the hydrogel. That is, when the G' value of the hydrogel was higher than 1.0 kPa, the cell proliferation was ceased and the proliferation cycle of cells was converged to G1 phase, whereas when the G' value was below 1.0 kPa, cell proliferation proceeded. By changing the G' value of hydrogels under encapsulation the cells, proliferation cycle of encapsulated mesenchymal stem cells was regulated to G1 phase and thus signal sensitivity were increased. 3-D polymer networks as hydrogels with tunable physical properties can be effectively used to control proliferation and lineage-restricted differentiation of stem cells. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jul 2015 · Biomaterials
    • "Controlled size and bidirectional architecture is of particular importance for musculoskeletal and neural tissue engineering, as they have been shown, in in vitro conditions, to synergistically control osteoblastic cell migration and differentiation[9], regulate tendon fibroblast growth and differentiation[10], enhance Table 3. Chronological advancements of imprint lithography in biomedicine. Study (year) Advancement of imprint lithography in biomedicine Ref.(1986)First in vitro study to demonstrate cell behaviour in response to imprinted patterns by electron beam lithography and photolithography[136]Chou et al.(1995)Introduction of nano-imprint lithography for the development of nano-scale features (sub- 25 nm)[137]Charest et al.(2004)First in vitro study to demonstrate cell behaviour in response to hot embossed imprinted patterns[138]Falconnet et al.(2004)Imprinting of protein patterns with nano-scale resolutions[139]Yim et al.(2007)First in vitro study to demonstrate stem cell lineage commitment on imprinted substrates[140]Reddy et al. (2011) In vitro inhibition of bacterial growth associated with catheter-associated urinary tract infection with the Sharklet Ò pattern[116]Prodanov et al. (2013) First in vivo study to demonstrate improved integration of imprinted medical devices[141]Marbacher et al. (2013) First example of using imprint lithography technology in the surgical setting[115]Magin et al. (2015) Development of micro-patterned lenses that prevent secondary cataract following surgery[142]Table 4. Indicative advancements of electrospinning, additive manufacturing and imprint lithography in biomedicine.Electrospinning Biodegradable synthetic polymers[7]Multiple[36]Bidirectionally aligned fibres[7]; controlled porosity[17,18]; precision down to 1.2 nm[6]Permanently differentiated cell phenotype maintenance[9,10]; control of stem cell lineage[16,123]Multiple[7]Additive manufacturing Biodegradable synthetic polymers64656667Ideally, through a hydrogel[81,82]The most precise 3D fabrication technology; precision down to 100 nm[3,4]Permanently differentiated cell phenotype maintenance[71,77]Primarily bone and cartilage[69,70,72]Imprint lithography Non-degradable synthetic polymers[91,92]Limited[92,110,111]The most precise 2D fabrication technology; precision down to 5 nm[5,96,97]Permanently differentiated cell phenotype maintenance[91,100]; control of stem cell lineage[140]N/A N/A: Not Available. "
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    ABSTRACT: Electrospinning, additive manufacturing and imprint lithography scaffold fabrication technologies have attracted great attention in biomedicine, as they allow production of two- and three- dimensional constructs with tuneable topographical and geometrical features. In vitro data demonstrate that electrospun and imprinted substrates offer control over permanently differentiated and stem cell function. Advancements in functionalisation strategies have further enhanced the bioactivity and reparative capacity of electrospun and additive manufactured devices, as has been evidenced in several preclinical models. Despite this overwhelming success in academic setting, only a few technologies have reached the clinic and only a fraction of them have become commercially available products.
    No preview · Article · Jun 2015 · Expert Review of Medical Devices
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